Variant 10-118009012-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000355624.8(RAB11FIP2):c.1525T>G(p.Phe509Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,458,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RAB11FIP2
ENST00000355624.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

RAB11FIP2 (HGNC:29152): (RAB11 family interacting protein 2) Enables protein homodimerization activity and protein kinase binding activity. Involved in several processes, including TRAM-dependent toll-like receptor 4 signaling pathway; phagocytosis; and positive regulation of GTPase activity. Located in endosome; nucleoplasm; and phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

RAB11FIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12901229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP2	NM_014904.3 linkuse as main transcript	c.1525T>G	p.Phe509Val	missense_variant	5/5	ENST00000355624.8	NP_055719.1
RAB11FIP2	NM_001330167.2 linkuse as main transcript	c.1585T>G	p.Phe529Val	missense_variant	6/6		NP_001317096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB11FIP2	ENST00000355624.8 linkuse as main transcript	c.1525T>G	p.Phe509Val	missense_variant	5/5	1	NM_014904.3	ENSP00000347839	P1	Q7L804-1
RAB11FIP2	ENST00000369199.5 linkuse as main transcript	c.1585T>G	p.Phe529Val	missense_variant	6/6	1		ENSP00000358200		Q7L804-2
RAB11FIP2	ENST00000476207.1 linkuse as main transcript	n.190+70T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250872

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458210

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000523

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.1525T>G (p.F509V) alteration is located in exon 5 (coding exon 5) of the RAB11FIP2 gene. This alteration results from a T to G substitution at nucleotide position 1525, causing the phenylalanine (F) at amino acid position 509 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.47

P;.

Vest4

0.21

MutPred

0.39

.;Gain of MoRF binding (P = 0.0727);

MVP

0.35

MPC

1.5

ClinPred

0.38

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over